Osteoarthritis (OA) is a complex, heterogeneous condition that is the most common cause of disability in the aging population. The hallmarks of the pathophysiology of OA are the breakdown of cartilage in joints and the associated changes in adjacent soft tissue and subchondral bone that lead to debilitating joint symptoms such as pain. The public health impact of OA, especially knee OA, has and will continue to increase dramatically, but there are no FDA-approved disease-modifying OA drugs (DMOADs), i.e., drugs designed to delay or avert the OA-related structural changes to cartilage and bone. Recent advances in magnetic resonance imaging (MRI) have been made, however, that have improved our understanding of the relationship between pathology and the structural changes to cartilage, subchondral bone and the surrounding soft tissues of the joint in OA. The proposed study builds on the strengths of two ongoing studies, the Osteoarthritis Initiative (OAI) and the Pivotal OAI MRI Analyses (POMA), an ancillary proposal to the OAI. The OAI was designed to address the lack of biomarkers for the development and progression of knee OA. Through POMA, we have utilized the OAI MRIs to identify imaging biomarkers of knee OA development and progression up to 48 months prior to the onset of radiographic knee OA (ROA). The overall objective of this proposal is to take advantage of a time-limited opportunity to build on our prior work and leverage the wealth of longitudinal data, including high-resolution MRI imaging at 3 Tesla(T), which has already been accumulated in the OAI. We will be able test whether structural changes detectable by MRI predict the onset of radiographic knee osteoarthritis (ROA) and the development of important clinical outcomes 24 months to 120 months later, and therefore much earlier in the disease course than currently established. A 120-month visit will be added to the OAI for participants with knees that did not have ROA at baseline. The specific aims are to identify imaging biomarkers of the development of incident radiographic knee OA (ROA) earlier in the disease course; and to identify the association of imaging biomarkers with changes in pain, function and performance associated with the onset of radiographic knee OA. Ultimately, this line of research will help to identify key risk factors for the development of OA and OA structural disease progression, and to identify potential targets for preventative and/or therapeutic interventions.